Last data update: Sep 23, 2024. (Total: 47723 publications since 2009)
Records 1-30 (of 173 Records) |
Query Trace: Gregory C [original query] |
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Demographic and clinical factors associated with bacterial or nonbacterial etiologies of acute undifferentiated febrile illness: Findings from a 3-year observational study in Thailand, 2017-2020
Wodniak NR , Bhengsri S , Skaggs B , Uttayamakul S , Sawatwong P , Sangwichian O , Gregory CJ , Chuenchom N , Peanumlom P , Khemla S , Lertwitayakumjorn T , Chaoprasert S , Piralam B , Simmali T , Chara C , Bloss E , MacArthur JR , Heffelfinger JD . Am J Trop Med Hyg 2024 111 (3) 650-660 Acute undifferentiated febrile illness (AUFI) is often undiagnosed in Thailand, resulting in delayed or ineffective treatment. We compared the demographic, exposure history, and clinical characteristics of AUFI patients with laboratory evidence of bacterial and nonbacterial pathogens. Patients aged 2-80 years presenting to 12 hospitals in Nakhon Phanom and Tak provinces were enrolled from April 2017 through May 2020. Interviews were conducted and blood, urine, and sputum were collected for culture as well as rapid diagnostic and molecular testing. A total of 1,263 patients tested positive for one or more bacterial, viral, or parasitic pathogens and were included in the analysis. Multivariable logistic regression was performed to compare factors associated with bacterial infections versus nonbacterial infections. Bacterial infections were more commonly identified in participants from Nakhon Phanom than Tak. Bacterial infections were independently associated with several factors including age ≥50 years (adjusted odds ratio [95% CI]): (4.18 [2.85-6.14]), contact with farm animals (1.82 [1.29-2.57]), antibiotic use within 72 hours of hospital presentation (2.37 [1.50-3.74]), jaundice (2.31 [1.15-4.63]), existing comorbidities (2.77 [1.93-3.96]), contact with febrile individuals (0.42 [0.31-0.57]), muscle pain (0.44 [0.31-0.64]), and rash (0.45 [0.29-0.70]). Bacterial infections were also associated with longer hospitalization (2.75 [2.08-3.64]) and lower odds of recovery at the time of discharge (0.14 [0.07-0.31]). Consideration of patient characteristics and signs/symptoms may help to inform targeted laboratory testing for suspected infectious etiologies. Understanding factors associated with bacterial and non-bacterial causes of AUFI may aid diagnosis and judicious use of antibiotics in resource-limited settings. |
Sudan Virus Disease among health care workers, Uganda, 2022
Wailagala A , Blair PW , Kobba K , Mubaraka K , Aanyu-Tumukahebwa H , Kiiza D , Sekikongo MT , Klena JD , Waitt P , Bahatungire RR , Kyobe HS , Atwine D , Adaku A , Bongomin B , Kirenga B , Boore A , Clark DV , Kaggwa D , Gregory M , Kabweru W , Kayondo W , Mbabazi SK , Kibuuka H , Kimuli I , Mulei S , Mutegeki M , Emmanuel B , Mwebesa H , Naluyima P , Okello S , Tumusiime A , Montgomery J , Vasireddy V , Olaro C , Wayengera M , Lamorde M . N Engl J Med 2024 391 (3) 285-287 |
U.S. stillbirth surveillance: The National Fetal Death File and other data sources
Gregory ECW , Barfield WD . Semin Perinatol 2023 151873 The National Vital Statistics System is the primary source of information on fetal deaths of 20 weeks of gestation or more in the United States. Data are cooperatively produced by jurisdiction vital statistics offices and the National Center for Health Statistics. In order to promote the uniformity of data, the National Center for Health Statistics issues The Model State Vital Statistics Act and Regulations, and produces standard certificates and reports, developed in collaboration with the states, to inform the development of jurisdictional vital records laws and regulations and data collection. While there are challenges in collecting national fetal death data, there are ongoing data quality improvement efforts to address them. Improved national fetal death data and data from other sources will continue to add insights into the risks, causes and prevention of fetal death. |
Profiling metal-induced genotoxic endpoints
Shoeb Mohammad , Zarus Gregory M , Abadin Henry E . J Environ Health 2023 86 (5) 30-35 Many toxic metals are involved in the initiation and progression of DNA damage that can result in the activation of DNA damage response machinery at double- and single-stranded DNA; this response can result in global and gene-specific DNA alteration. The toxicological profiles from the Agency for Toxic Substances and Disease Registry (ATSDR) and several other studies have demonstrated the influence of metal exposure-induced genotoxic endpoints and epigenetic modifications. Our review systematically summarizes accumulating evidence from ATSDR toxicological profiles and the available literature that demonstrate a possible induction of various genotoxic endpoints and metal exposures. We include in this article studies on chromium, arsenic, nickel, lead, mercury, and zinc. |
Expansion of invasive group A streptococcus M1(uk) lineage in active bacterial core surveillance, United States, 2019‒2021
Li Y , Rivers J , Mathis S , Li Z , Chochua S , Metcalf BJ , Beall B , Onukwube J , Gregory CJ , McGee L . Emerg Infect Dis 2023 29 (10) 2116-2120 From 2015-2018 to 2019‒2021, hypertoxigenic M1(UK) lineage among invasive group A Streptococcus increased in the United States (1.7%, 21/1,230 to 11%, 65/603; p<0.001). M1(UK) was observed in 9 of 10 states, concentrated in Georgia (n = 41), Tennessee (n = 13), and New York (n = 13). Genomic cluster analysis indicated recent expansions. |
Pharyngeal co-infections with monkeypox virus and group A streptococcus, United States, 2022
Kaiser RM , Cash-Goldwasser S , Lehnertz N , Griffith J , Ruprecht A , Stanton J , Feldpausch A , Pavlick J , Bruen CA , Perez-Molinar D , Peglow SR , Akinsete OO , Morris SB , Raizes E , Gregory C , Lynfield R . Emerg Infect Dis 2023 29 (9) 1855-1858 We report 2 cases of pharyngeal monkeypox virus and group A Streptococcus co-infection in the United States. No rash was observed when pharyngitis symptoms began. One patient required intubation before mpox was diagnosed. Healthcare providers should be aware of oropharyngeal mpox manifestations and possible co-infections; early treatment might prevent serious complications. |
Tracing the origin of SARS-CoV-2 Omicron-like Spike sequences detected in wastewater (preprint)
Shafer MM , Bobholz MJ , Vuyk WC , Gregory D , Roguet A , Haddock Soto LA , Rushford C , Janssen KH , Ries HJ , Pilch HE , Mullen PA , Fahney RB , Wei W , Lambert M , Wenzel J , Halfmann P , Kawaoka Y , Wilson NA , Friedrich TC , Pray IW , Westergaard R , O'Connor DH , Johnson MC . medRxiv 2022 31 Background: The origin of divergent SARS-CoV-2 spike sequences found in wastewater, but not in clinical surveillance, remains unclear. These "cryptic" wastewater sequences have harbored many of the same mutations that later emerged in Omicron lineages. We first detected a cryptic lineage in municipal wastewater in Wisconsin in January 2022. Named the "Wisconsin Lineage", we sought to determine this virus's geographic origin and characterize its persistence and evolution over time. Method(s): We systematically sampled maintenance holes to trace the Wisconsin Lineage's origin. We sequenced spike RBD domains, and where possible, whole viral genomes, to characterize the evolution of this lineage over the 13 consecutive months that it was detectable. Finding(s): The persistence of the Wisconsin Lineage signal allowed us to trace it from a central wastewater plant to a single facility, with a high concentration of viral RNA. The viral sequences contained a combination of fixed nucleotide substitutions characteristic of Pango lineage B.1.234, which circulated in Wisconsin at low levels from October 2020 to February 2021, while mutations in the spike gene resembled those subsequently found in Omicron variants. Interpretation(s): We propose that prolonged detection of the Wisconsin Lineage in wastewater represents persistent shedding of SARS-CoV-2 from an infected individual, with ongoing within-host viral evolution leading to an ancestral B.1.234 virus accumulating "Omicron-like" mutations. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. |
Cryptic transmission of SARS-CoV-2 in Washington State.
Bedford T , Greninger AL , Roychoudhury P , Starita LM , Famulare M , Huang ML , Nalla A , Pepper G , Reinhardt A , Xie H , Shrestha L , Nguyen TN , Adler A , Brandstetter E , Cho S , Giroux D , Han PD , Fay K , Frazar CD , Ilcisin M , Lacombe K , Lee J , Kiavand A , Richardson M , Sibley TR , Truong M , Wolf CR , Nickerson DA , Rieder MJ , Englund JA , Hadfield J , Hodcroft EB , Huddleston J , Moncla LH , Müller NF , Neher RA , Deng X , Gu W , Federman S , Chiu C , Duchin J , Gautom R , Melly G , Hiatt B , Dykema P , Lindquist S , Queen K , Tao Y , Uehara A , Tong S , MacCannell D , Armstrong GL , Baird GS , Chu HY , Shendure J , Jerome KR . medRxiv 2020 Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding. |
Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers - Eight U.S. Locations, December 2020-March 2021.
Thompson MG , Burgess JL , Naleway AL , Tyner HL , Yoon SK , Meece J , Olsho LEW , Caban-Martinez AJ , Fowlkes A , Lutrick K , Kuntz JL , Dunnigan K , Odean MJ , Hegmann KT , Stefanski E , Edwards LJ , Schaefer-Solle N , Grant L , Ellingson K , Groom HC , Zunie T , Thiese MS , Ivacic L , Wesley MG , Lamberte JM , Sun X , Smith ME , Phillips AL , Groover KD , Yoo YM , Gerald J , Brown RT , Herring MK , Joseph G , Beitel S , Morrill TC , Mak J , Rivers P , Harris KM , Hunt DR , Arvay ML , Kutty P , Fry AM , Gaglani M . MMWR Morb Mortal Wkly Rep 2021 70 (13) 495-500 Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials (1,2); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood. Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight U.S. locations during December 14, 2020-March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19-associated illness. Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (62.8%) received both recommended mRNA doses and 477 (12.1%) received only one dose of mRNA vaccine.(†) Among unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) per 1,000 person-days.(§) In contrast, among fully immunized (≥14 days after second dose) persons, 0.04 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 0.19 infections per 1,000 person-days were reported. Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization. These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions. COVID-19 vaccination is recommended for all eligible persons. |
Correction: A collaborative translational research framework for evaluating and implementing the appropriate use of human genome sequencing to improve health.
Khoury MJ , Feero WG , Chambers DA , Brody LC , Aziz N , Green RC , Janssens Acjw , Murray MF , Rodriguez LL , Rutter JL , Schully SD , Winn DM , Mensah GA . PLoS Med 2018 15 (8) e1002650 The fourth author’s name is incorrect. The correct name is Lawrence C. Brody. The correct citation is: Khoury MJ, Feero WG, Chambers DA, Brody LC, Aziz N, Green RC, et al. (2018) A collaborative translational research framework for evaluating and implementing the appropriate use of human genome sequencing to improve health. PLoS Med 15(8): e1002631. https://doi.org/10.1371/journal.pmed.1002631. |
Adapterama II: universal amplicon sequencing on Illumina platforms (TaggiMatrix).
Glenn TC , Pierson TW , Bayona-Vásquez NJ , Kieran TJ , Hoffberg SL , Thomas Iv JC , Lefever DE , Finger JW , Gao B , Bian X , Louha S , Kolli RT , Bentley KE , Rushmore J , Wong K , Shaw TI , Rothrock MJ Jr , McKee AM , Guo TL , Mauricio R , Molina M , Cummings BS , Lash LH , Lu K , Gilbert GS , Hubbell SP , Faircloth BC . PeerJ 2019 7 e7786 Next-generation sequencing (NGS) of amplicons is used in a wide variety of contexts. In many cases, NGS amplicon sequencing remains overly expensive and inflexible, with library preparation strategies relying upon the fusion of locus-specific primers to full-length adapter sequences with a single identifying sequence or ligating adapters onto PCR products. In Adapterama I, we presented universal stubs and primers to produce thousands of unique index combinations and a modifiable system for incorporating them into Illumina libraries. Here, we describe multiple ways to use the Adapterama system and other approaches for amplicon sequencing on Illumina instruments. In the variant we use most frequently for large-scale projects, we fuse partial adapter sequences (TruSeq or Nextera) onto the 5' end of locus-specific PCR primers with variable-length tag sequences between the adapter and locus-specific sequences. These fusion primers can be used combinatorially to amplify samples within a 96-well plate (8 forward primers + 12 reverse primers yield 8 × 12 = 96 combinations), and the resulting amplicons can be pooled. The initial PCR products then serve as template for a second round of PCR with dual-indexed iTru or iNext primers (also used combinatorially) to make full-length libraries. The resulting quadruple-indexed amplicons have diversity at most base positions and can be pooled with any standard Illumina library for sequencing. The number of sequencing reads from the amplicon pools can be adjusted, facilitating deep sequencing when required or reducing sequencing costs per sample to an economically trivial amount when deep coverage is not needed. We demonstrate the utility and versatility of our approaches with results from six projects using different implementations of our protocols. Thus, we show that these methods facilitate amplicon library construction for Illumina instruments at reduced cost with increased flexibility. A simple web page to design fusion primers compatible with iTru primers is available at: http://baddna.uga.edu/tools-taggi.html. A fast and easy to use program to demultiplex amplicon pools with internal indexes is available at: https://github.com/lefeverde/Mr_Demuxy. |
Notes from the field: Increase in pediatric invasive group A streptococcus infections - Colorado and Minnesota, October-December 2022
Gregory CJ , Chochua S , Onukwube J , Arvay M . MMWR Morb Mortal Wkly Rep 2023 72 (10) 265-267 During fall 2022, a resurgence of invasive group A Streptococcus (iGAS) infection in children and adolescents was observed in two of CDC’s Emerging Infections Program (EIP)* surveillance sites: Colorado (Denver metropolitan area) and Minnesota (entire state). This increase followed historic declines in invasive bacterial diseases during 2020, concurrent with mitigation strategies implemented during the COVID-19 pandemic† (1). Whereas reports of iGAS increased among all age groups, including adults, the increase among children and adolescents was notable, occurred earlier than seasonal increases during previous years, and accompanied a resurgence in hospitalizations for respiratory viral illnesses such as respiratory syncytial virus (RSV) and influenza. Viral infections, such as influenza and varicella, have been identified as risk factors for iGAS infection in children, adolescents, and adults (2) and can be reduced by vaccination. |
In-hospital mortality risk stratification in children under 5 years old with pneumonia with or without pulse oximetry: A secondary analysis of the Pneumonia REsearch Partnership To Assess WHO REcommendations (PREPARE) dataset
Hooli S , King C , McCollum ED , Colbourn T , Lufesi N , Mwansambo C , Gregory CJ , Thamthitiwat S , Cutland C , Madhi SA , Nunes MC , Gessner BD , Hazir T , Mathew JL , Addo-Yobo E , Chisaka N , Hassan M , Hibberd PL , Jeena P , Lozano JM , MacLeod WB , Patel A , Thea DM , Nguyen NTV , Zaman SM , Ruvinsky RO , Lucero M , Kartasasmita CB , Turner C , Asghar R , Banajeh S , Iqbal I , Maulen-Radovan I , Mino-Leon G , Saha SK , Santosham M , Singhi S , Awasthi S , Bavdekar A , Chou M , Nymadawa P , Pape JW , Paranhos-Baccala G , Picot VS , Rakoto-Andrianarivelo M , Rouzier V , Russomando G , Sylla M , Vanhems P , Wang J , Basnet S , Strand TA , Neuman MI , Arroyo LM , Echavarria M , Bhatnagar S , Wadhwa N , Lodha R , Aneja S , Gentile A , Chadha M , Hirve S , O'Grady KF , Clara AW , Rees CA , Campbell H , Nair H , Falconer J , Williams LJ , Horne M , Qazi SA , Nisar YB . Int J Infect Dis 2023 129 240-250 OBJECTIVES: We determined pulse oximetry benefit in pediatric pneumonia mortality-risk stratification and chest indrawing pneumonia in-hospital mortality risk factors. METHODS: We report characteristics and in-hospital pneumonia-related mortality of children 2-59-months-old included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest indrawing pneumonia to identify mortality risk factors. RESULTS: Among 285,839 children, 164,244 (57·5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5·8%, 95% CI 5·6-5·9% vs 2·1%, 95% CI 1·9-2·4%). One in five children with chest indrawing pneumonia was hypoxemic (19·7%, 95% CI 19·0-20·4%) and the hypoxemic CFR was 10·3% (95% CI 9·1%-11·5%). Other mortality risk factors were younger age (either 2-5 months (aOR 9·94, 95% CI 6·67-14·84) or 6-11 months (aOR 2·67, 95% CI 1·71-4·16)), moderate malnutrition (aOR 2·41, 95% CI 1·87-3·09), and female sex (aOR 1·82, 95% CI 1·43-2·32). CONCLUSIONS: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest indrawing pneumonia were hypoxemic and one in ten died. Young age and moderate malnutrition were risk factors for in-hospital chest indrawing pneumonia-related mortality. Pulse oximetry should be integrated in under-five pneumonia hospital care. |
Dispersion of modified fumed silica in elastomeric nanocomposites
Okoli Ugochukwu , Rishi Kabir , Beaucage Gregory , Kammler Hendrik K , McGlasson Alex , Chauby Michael , Narayanan Vishak , Grammens James , Kuppa Vikram K . Polymer 2023 264 125407 In polymer nanocomposites, surface modification of silica aggregates can shield Coulombic interactions that inhibit agglomeration and formation of a network of agglomerates. Surface modification is usually achieved with silane coupling agents although carbon-coating during pyrolytic silica production is also possible. Pyrogenic silica with varying surface carbon contents were dispersed in styrene-butadiene (SBR) rubber to explore the impact on hierarchical dispersion, the emergence of meso-scale structures, and the rheological response. Pristine pyrogenic silica aggregates at concentrations above a critical value (related to the Debye screening length) display correlated meso-scale structures and poor filler network formation in rubber nanocomposites due to the presence of silanol groups on the surface. In the present study, flame synthesized silica with sufficient surface carbon monolayers can mitigate the charge repulsion thereby impacting network structural emergence. The impact of the surface carbon on the van der Waals enthalpic attraction, a∗, is determined. The van der Waals model for polymer nanocomposites is drawn through an analogy between thermal energy, kBT, and the accumulated strain, γ. The rheological response of the emergent meso-scale structures depends on the surface density of both carbon and silanol groups. |
Assembling a global database of child pneumonia studies to inform WHO pneumonia management algorithm: Methodology and applications
Martin H , Falconer J , Addo-Yobo E , Aneja S , Arroyo LM , Asghar R , Awasthi S , Banajeh S , Bari A , Basnet S , Bavdekar A , Bhandari N , Bhatnagar S , Bhutta ZA , Brooks A , Chadha M , Chisaka N , Chou M , Clara AW , Colbourn T , Cutland C , D'Acremont V , Echavarria M , Gentile A , Gessner B , Gregory CJ , Hazir T , Hibberd PL , Hirve S , Hooli S , Iqbal I , Jeena P , Kartasasmita CB , King C , Libster R , Lodha R , Lozano JM , Lucero M , Lufesi N , MacLeod WB , Madhi SA , Mathew JL , Maulen-Radovan I , McCollum ED , Mino G , Mwansambo C , Neuman MI , Nguyen NTV , Nunes MC , Nymadawa P , O'Grady KF , Pape JW , Paranhos-Baccala G , Patel A , Picot VS , Rakoto-Andrianarivelo M , Rasmussen Z , Rouzier V , Russomando G , Ruvinsky RO , Sadruddin S , Saha SK , Santosham M , Singhi S , Soofi S , Strand TA , Sylla M , Thamthitiwat S , Thea DM , Turner C , Vanhems P , Wadhwa N , Wang J , Zaman SM , Campbell H , Nair H , Qazi SA , Nisar YB . J Glob Health 2022 12 04075 BACKGROUND: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines. METHODS: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set. RESULTS: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285839 children with pneumonia (244323 in the hospital and 41516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285839 episodes, 280998 occurred in children 0-59 months old, of which 129584 (46%) were 2-11 months of age and 152730 (54%) were males. CONCLUSIONS: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly. |
Improving community coverage of Japanese encephalitis vaccination: lessons learned from a mass campaign in Battambang Province, Cambodia
Thigpen MC , Sarath S , Soeung SC , Vichit O , Kitsutani P , Sandhu H , Gregory C , Fischer M , Morn C , Hills SL . BMC Public Health 2022 22 (1) 2244 A mass Japanese encephalitis (JE) immunization campaign for children aged 9 months through 12 years was conducted in 2013 in Battambang province, western Cambodia. Vaccinators working at almost 2,000 immunization posts in approximately 800 villages provided vaccinations to almost 310,000 children using one dose of Chengdu Institute of Biological Products' live, attenuated SA14-14-2 JE vaccine (CD-JEV), achieving a coverage rate of greater than 90%. Lessons learned, in general for mass vaccination campaigns and specifically for vaccination with CD-JEV, are described. These observations will be of benefit for public health officials and to help inform planning for future campaigns for JE or other vaccine-preventable diseases in Cambodia and elsewhere. |
Changes in home births by race and hispanic origin and state of residence of mother: United States, 2019-2020 and 2020- 2021
Gregory EC , Osterman MJ , Valenzuela CP . Natl Vital Stat Rep 2022 71 (8) 1-10 Objectives-This report describes changes between 2020 and 2021 in the percentage of home births by month, race and Hispanic origin, and state of residence of the mother, and makes comparisons with changes occurring between 2019 and 2020. |
New web-based public health assessment guidance manual: A foundational tool for evaluating exposure and public health impacts in communities
Ulirsch Gregory V , Zheng Li . J Environ Health 2022 85 (2) 38-41 The article discusses the Agency for Toxic Substances and Disease Registry's (ATSDR) activities for better understanding of hazardous substances and protection of public health in 2022. Topics covered include updating the public health assessment guidance manual (PGHAM), its basic components, and the new e-manual's six main sections. Also noted is the largest section Conducting Scientific Evaluations in the manual with its four subsections. |
Factors impacting survival in those transplanted for NASH cirrhosis: Data from the NailNASH Consortium
Rinella ME , Satapathy SK , Brandman D , Smith C , Elwir S , Xia J , Gibson M , Figueredo C , Angirekula M , Vanatta JM , Sarwar R , Jiang Y , Gregory D , Agostini T , Ko J , Podila P , Gallo G , Watt KD , Siddiqui MS . Clin Gastroenterol Hepatol 2022 21 (2) 445-455 e2 BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is the leading indication for liver transplant (LT) in women and the elderly. Granular details into factors impacting survival in this population are needed to optimize management and improve outcomes. METHODS: Patients receiving LT for NASH cirrhosis from 1997 to 2017 across 7 transplant centers (NailNASH consortium) were analyzed. The primary outcome was all-cause mortality, and causes of death were enumerated. All outcomes were cross referenced with United Network for Organ Sharing and adjudicated at each individual center. Cox regression models were constructed to elucidate clinical factors impacting mortality. RESULTS: Nine hundred thirty-eight patients with a median follow-up of 3.8 years (interquartile range, 1.60-7.05 years) were included. The 1-, 3-, 5-, 10-, and 15-year survival of the cohort was 93%, 88%, 83%, 69%, and 46%, respectively. Of 195 deaths in the cohort, the most common causes were infection (19%), cardiovascular disease (18%), cancer (17%), and liver-related (11%). Inferior survival was noted in patients >65 years. On multivariable analysis, age >65 (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.04-2.77; P = .04), end-stage renal disease (HR, 1.55; 95% CI, 1.04-2.31; P = .03), black race (HR, 5.25; 95% CI, 2.12-12.96; P = .0003), and non-calcineurin inhibitors-based regimens (HR, 2.05; 95% CI, 1.19-3.51; P = .009) were associated with increased mortality. Statin use after LT favorably impacted survival (HR, 0.38; 95% CI, 0.19-0.75; P = .005). CONCLUSIONS: Despite excellent long-term survival, patients transplanted for NASH at >65 years or with type 2 diabetes mellitus at transplant had higher mortality. Statin use after transplant attenuated risk and was associated with improved survival across all subgroups, suggesting that careful patient selection and implementation of protocol-based management of metabolic comorbidities may further improve clinical outcomes. |
Sustaining Maternal and Neonatal Tetanus Elimination (MNTE) in countries that have been validated for elimination - progress and challenges
Yusuf N , Steinglass R , Gasse F , Raza A , Ahmed B , Blanc DC , Yakubu A , Gregory C , Tohme RA . BMC Public Health 2022 22 (1) 691 BACKGROUND: As of October 2021, 47 (80%) of the 59 countries, identified at highest risk for Maternal and Neonatal Tetanus (MNT), had been validated for elimination. We assessed sustainability of MNT elimination (MNTE) in 28 countries that were validated during 2011‒2020. METHODS: We assessed the attainment of the following MNTE sustainability indicators: 1) ≥ 90% coverage with three doses of Diphtheria-Tetanus-Pertussis vaccine (DTP3) among infants < 1 year, 2) ≥ 80% coverage with at least two doses of tetanus toxoid-containing vaccine (TTCV2 +) among pregnant women, 3) ≥ 80% protection at birth (PAB), 4) ≥ 70% skilled birth attendance (SBA), and 4) ≥ 80% first (ANC1) and fourth antenatal care (ANC4) visits. We assessed the introduction of TTCV booster doses. Data sources included the 2020 WHO /UNICEF Joint Reporting Forms, and the latest Demographic and Health Survey (DHS) or Multi-Indicator Cluster Surveys (MICS) for each country, if available. We reviewed literature and used DHS/MICS data to identify barriers to sustaining MNTE. RESULTS: Of 28 assessed countries, 7 (25%) reported ≥ 90% DTP3 coverage, 4 of 26 (16%) reported ≥ 80% TTCV2 + coverage, and 23 of 27 (85%) reported ≥ 80% PAB coverage. Based on DHS/MICS in 15 of the 28 countries, 10 (67%) achieved ≥ 70% SBA delivery, 13 (87%) achieved ≥ 80% ANC1 visit coverage, and 3 (20%) ≥ 80% ANC4 visit coverage. We observed sub-optimal coverage in many countries at the subnational level. The first, second and third booster doses of TTCV respectively have been introduced in 6 (21%), 5 (18%), and 1 (4%) of 28 countries. Only three countries conducted post-MNTE validation assessments. Barriers to MNTE sustainability included: competing program priorities, limited resources to introduce TTCV booster doses and implement corrective immunization in high-risk districts and socio-economic factors. CONCLUSIONS: Despite good performance of MNTE indicators in several countries, MNTE sustainability appears threatened in some countries. Integration and coordination of MNTE activities with other immunization activities in the context of the Immunization Agenda 2030 lifecourse vaccination strategy such as providing tetanus booster doses in school-based vaccination platforms, during measles second dose and HPV vaccination, and integrating MNTE post-validation assessments with immunization program reviews will ensure MNTE is sustained. |
Notes from the Field: Early Evidence of the SARS-CoV-2 B.1.1.529 (Omicron) Variant in Community Wastewater - United States, November-December 2021.
Kirby AE , Welsh RM , Marsh ZA , Yu AT , Vugia DJ , Boehm AB , Wolfe MK , White BJ , Matzinger SR , Wheeler A , Bankers L , Andresen K , Salatas C , Gregory DA , Johnson MC , Trujillo M , Kannoly S , Smyth DS , Dennehy JJ , Sapoval N , Ensor K , Treangen T , Stadler LB , Hopkins L . MMWR Morb Mortal Wkly Rep 2022 71 (3) 103-105 The United States designated the B.1.1.529 (Omicron) variant of SARS-CoV-2 (the virus that causes COVID-19) a variant of concern on November 30, 2021, and the first U.S. Omicron COVID-19 case was reported on December 1 (1). By December 18, Omicron was estimated to account for 37.9% of U.S. COVID-19 cases.* Early warning systems, such as sewage (wastewater) surveillance,† can help track the spread of SARS-CoV-2 variants across communities (2). | | The National Wastewater Surveillance System (NWSS) comprises 43 health departments funded by CDC to provide data on presence of and trends in SARS-CoV-2 infections that are independent of clinical testing. In addition to total SARS-CoV-2 testing, some health departments track SARS-CoV-2 variants by detecting variant-associated mutations in wastewater. Health departments in four states (California, Colorado, New York, and Texas) were the first wastewater surveillance programs to detect evidence of Omicron in community wastewater. This report describes the initial detections in wastewater during November 21–December 16, 2021, and the interpretative framework for these types of data. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.§ |
Rethinking public health campaigns in the COVID-19 era: a call to improve effectiveness, equity and impact
Jafari H , Saarlas KN , Schluter WW , Espinal M , Ijaz K , Gregory C , Filler S , Wolff C , Krause LK , O'Brien K , Pearson L , Gupta A , Rebollo Polo M , Shuaib F . BMJ Glob Health 2021 6 (11) Health campaigns are time-bound, intermittent activities that address specific epidemiological challenges, expediently fill delivery gaps or provide surge coverage for health interventions. | They can be used to prevent or respond to disease outbreaks, control or eliminate targeted diseases as a public health problem, eradicate a disease altogether or achieve other health goals. | In 2020, more than 530 health campaigns were planned for 26 different interventions representing 13 diseases and 105 countries. | Due to the COVID-19 pandemic, by the end of last year, about half of planned campaigns were postponed, cancelled, or suspended leaving hundreds of millions of children and families at risk of vaccine-preventable diseases, tropical diseases and malnutrition. | So far in 2021, more than 280 campaigns have been cancelled or delayed. | As health campaigns restart and catch up on the delivery of missed drugs, vaccines and nutritional supplements, and countries roll out COVID-19 vaccines, there is an opportunity to rethink the way we plan and implement campaigns to improve their effectiveness and impact. | |
Descriptive Evaluation of Antibody Responses to SARS-CoV-2 Infection in Plasma and Gingival Crevicular Fluid in a Nursing Home Cohort-Arkansas, June-August 2020.
Brown NE , Lyons AK , Schuh AJ , Stumpf MM , Harcourt JL , Tamin A , Rasheed MAU , Mills L , Lester SN , Thornburg NJ , Nguyen K , Costantini V , Vinjé J , Huang JY , Gilbert SE , Gable P , Bollinger S , Sabour S , Beshearse E , Surie D , Biedron C , Gregory CJ , Clemmons NS , Whitaker B , Coughlin MM , Seely KA , Garner K , Gulley T , Haney T , Kothari A , Patil N , Halpin AL , McDonald LC , Kutty PK , Brown AC . Infect Control Hosp Epidemiol 2021 43 (11) 1-24 OBJECTIVE: Characterize and compare SARS-CoV-2-specific immune responses in plasma and gingival crevicular fluid (GCF) from nursing home residents during and after natural infection. DESIGN: Prospective cohort. SETTING: Nursing home. PARTICIPANTS: SARS-CoV-2-infected nursing home residents. METHODS: A convenience sample of 14 SARS-CoV-2-infected nursing home residents, enrolled 4-13 days after real-time reverse transcription polymerase chain reaction diagnosis, were followed for 42 days. Post diagnosis, plasma SARS-CoV-2-specific pan-Immunoglobulin (Ig), IgG, IgA, IgM, and neutralizing antibodies were measured at 5 timepoints and GCF SARS-CoV-2-specific IgG and IgA were measured at 4 timepoints. RESULTS: All participants demonstrated immune responses to SARS-CoV-2 infection. Among 12 phlebotomized participants, plasma was positive for pan-Ig and IgG in all 12, neutralizing antibodies in 11, IgM in 10, and IgA in 9. Among 14 participants with GCF specimens, GCF was positive for IgG in 13 and IgA in 12. Immunoglobulin responses in plasma and GCF had similar kinetics; median times to peak antibody response was similar across specimen types (4 weeks for IgG; 3 weeks for IgA). Participants with pan-Ig, IgG, and IgA detected in plasma and GCF IgG remained positive through this evaluation's end 46-55 days post-diagnosis. All participants were viral culture negative by the first detection of antibodies. CONCLUSIONS: Nursing home residents had detectable SARS-CoV-2 antibodies in plasma and GCF after infection. Kinetics of antibodies detected in GCF mirrored those from plasma. Non-invasive GCF may be useful for detecting and monitoring immunologic responses in populations unable or unwilling to be phlebotomized. |
Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines.
Thompson MG , Burgess JL , Naleway AL , Tyner H , Yoon SK , Meece J , Olsho LEW , Caban-Martinez AJ , Fowlkes AL , Lutrick K , Groom HC , Dunnigan K , Odean MJ , Hegmann K , Stefanski E , Edwards LJ , Schaefer-Solle N , Grant L , Ellingson K , Kuntz JL , Zunie T , Thiese MS , Ivacic L , Wesley MG , Mayo Lamberte J , Sun X , Smith ME , Phillips AL , Groover KD , Yoo YM , Gerald J , Brown RT , Herring MK , Joseph G , Beitel S , Morrill TC , Mak J , Rivers P , Poe BP , Lynch B , Zhou Y , Zhang J , Kelleher A , Li Y , Dickerson M , Hanson E , Guenther K , Tong S , Bateman A , Reisdorf E , Barnes J , Azziz-Baumgartner E , Hunt DR , Arvay ML , Kutty P , Fry AM , Gaglani M . N Engl J Med 2021 385 (4) 320-329 BACKGROUND: Information is limited regarding the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in attenuating coronavirus disease 2019 (Covid-19) when administered in real-world conditions. METHODS: We conducted a prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers. From December 14, 2020, to April 10, 2021, the participants completed weekly SARS-CoV-2 testing by providing mid-turbinate nasal swabs for qualitative and quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis. The formula for calculating vaccine effectiveness was 100% × (1 - hazard ratio for SARS-CoV-2 infection in vaccinated vs. unvaccinated participants), with adjustments for the propensity to be vaccinated, study site, occupation, and local viral circulation. RESULTS: SARS-CoV-2 was detected in 204 participants (5%), of whom 5 were fully vaccinated (≥14 days after dose 2), 11 partially vaccinated (≥14 days after dose 1 and <14 days after dose 2), and 156 unvaccinated; the 32 participants with indeterminate vaccination status (<14 days after dose 1) were excluded. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower (relative risk, 0.42; 95% CI, 0.18 to 0.98) and the duration of illness was shorter, with 2.3 fewer days spent sick in bed (95% CI, 0.8 to 3.7). CONCLUSIONS: Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infection when administered in real-world conditions, and the vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination. (Funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention.). |
COVID-19 Vaccine Breakthrough Infections Reported to CDC - United States, January 1-April 30, 2021.
CDC COVID-19 Vaccine Breakthrough Case Investigations Team , Birhane Meseret , Bressler Sara , Chang Gregory , Clark Thomas , Dorough Layne , Fischer Marc , Watkins Louise Francois , Goldstein Jason M , Kugeler Kiersten , Langley Gayle , Lecy Kristin , Martin Stacey , Medalla Felicita , Mitruka Kiren , Nolen Leisha , Sadigh Katrin , Spratling Robin , Thompson Gail , Trujillo Alma . MMWR Morb Mortal Wkly Rep 2021 70 (21) 792-793 COVID-19 vaccines are a critical tool for controlling the ongoing global pandemic. The Food and Drug Administration (FDA) has issued Emergency Use Authorizations for three COVID-19 vaccines for use in the United States.* In large, randomized-controlled trials, each vaccine was found to be safe and efficacious in preventing symptomatic, laboratory-confirmed COVID-19 (1-3). Despite the high level of vaccine efficacy, a small percentage of fully vaccinated persons (i.e. received all recommended doses of an FDA-authorized COVID-19 vaccine) will develop symptomatic or asymptomatic infections with SARS-CoV-2, the virus that causes COVID-19 (2-8). |
The Impact of Covid-19 State Closure Orders on Consumer Spending, Employment, and Business Revenue.
Dunphy C , Miller GF , Rice K , Vo L , Sunshine G , McCord R , Howard-Williams M , Coronado F . J Public Health Manag Pract 2021 28 (1) 43-49 CONTEXT: In response to the COVID-19 pandemic, states across the United States implemented various strategies to mitigate transmission of SARS-CoV-2 (the virus that causes COVID-19). OBJECTIVE: To examine the effect of COVID-19-related state closures on consumer spending, business revenue, and employment, while controlling for changes in COVID-19 incidence and death. DESIGN: The analysis estimated a difference-in-difference model, utilizing temporal and geographic variation in state closure orders to analyze their impact on the economy, while controlling for COVID-19 incidence and death. PARTICIPANTS: State-level data on economic outcomes from the Opportunity Insights data tracker and COVID-19 cases and death data from usafacts.org. INTERVENTIONS: The mitigation strategy analyzed within this study was COVID-19-related state closure orders. Data on these orders were obtained from state government Web sites containing executive or administrative orders. MAIN OUTCOME MEASURES: Outcomes include state-level estimates of consumer spending, business revenue, and employment levels. RESULTS: Analyses showed that although state closures led to a decrease in consumer spending, business revenue, and employment, they accounted for only a small portion of the observed decreases in these outcomes over the first wave of COVID-19. CONCLUSIONS: The impact of COVID-19 on economic activity likely reflects a combination of factors, in addition to state closures, such as individuals' perceptions of risk related to COVID-19 incidence, which may play significant roles in impacting economic activity. |
Interim Estimates of Vaccine Effectiveness of Pfizer-BioNTech and Moderna COVID-19 Vaccines Among Health Care Personnel - 33 U.S. Sites, January-March 2021.
Pilishvili T , Fleming-Dutra KE , Farrar JL , Gierke R , Mohr NM , Talan DA , Krishnadasan A , Harland KK , Smithline HA , Hou PC , Lee LC , Lim SC , Moran GJ , Krebs E , Steele M , Beiser DG , Faine B , Haran JP , Nandi U , Schrading WA , Chinnock B , Henning DJ , LoVecchio F , Nadle J , Barter D , Brackney M , Britton A , Marceaux-Galli K , Lim S , Phipps EC , Dumyati G , Pierce R , Markus TM , Anderson DJ , Debes AK , Lin M , Mayer J , Babcock HM , Safdar N , Fischer M , Singleton R , Chea N , Magill SS , Verani J , Schrag S . MMWR Morb Mortal Wkly Rep 2021 70 (20) 753-758 Throughout the COVID-19 pandemic, health care personnel (HCP) have been at high risk for exposure to SARS-CoV-2, the virus that causes COVID-19, through patient interactions and community exposure (1). The Advisory Committee on Immunization Practices recommended prioritization of HCP for COVID-19 vaccination to maintain provision of critical services and reduce spread of infection in health care settings (2). Early distribution of two mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) to HCP allowed assessment of the effectiveness of these vaccines in a real-world setting. A test-negative case-control study is underway to evaluate mRNA COVID-19 vaccine effectiveness (VE) against symptomatic illness among HCP at 33 U.S. sites across 25 U.S. states. Interim analyses indicated that the VE of a single dose (measured 14 days after the first dose through 6 days after the second dose) was 82% (95% confidence interval [CI] = 74%-87%), adjusted for age, race/ethnicity, and underlying medical conditions. The adjusted VE of 2 doses (measured ≥7 days after the second dose) was 94% (95% CI = 87%-97%). VE of partial (1-dose) and complete (2-dose) vaccination in this population is comparable to that reported from clinical trials and recent observational studies, supporting the effectiveness of mRNA COVID-19 vaccines against symptomatic disease in adults, with strong 2-dose protection. |
COVID-19 response by the Hopi Tribe: impact of systems improvement during the first wave on the second wave of the pandemic.
Humeyestewa D , Burke RM , Kaur H , Vicenti D , Jenkins R , Yatabe G , Hirschman J , Hamilton J , Fazekas K , Leslie G , Sehongva G , Honanie K , Tu'tsi E , Mayer O , Rose MA , Diallo Y , Damon S , Zilversmit Pao L , McCraw HM , Talawyma B , Herne M , Nuvangyaoma TL , Welch S , Balajee SA . BMJ Glob Health 2021 6 (5) The Hopi Tribe is a sovereign nation home to ~7500 Hopi persons living primarily in 12 remote villages. The Hopi Tribe, like many other American Indian nations, has been disproportionately affected by COVID-19. On 18 May 2020, a team from the US Centers for Disease Control and Prevention (CDC) was deployed on the request of the tribe in response to increases in COVID-19 cases. Collaborating with Hopi Health Care Center (the reservation's federally run Indian Health Service health facility) and CDC, the Hopi strengthened public health systems and response capacity from May to August including: (1) implementing routine COVID-19 surveillance reporting; (2) establishing the Hopi Incident Management Authority for rapid coordination and implementation of response activities across partners; (3) implementing a community surveillance programme to facilitate early case detection and educate communities on COVID-19 prevention; and (4) applying innovative communication strategies to encourage mask wearing, hand hygiene and physical distancing. These efforts, as well as community adherence to mitigation measures, helped to drive down cases in August. As cases increased in September-November, the improved capacity gained during the first wave of the pandemic enabled the Hopi leadership to have real-time awareness of the changing epidemiological landscape. This prompted rapid response coordination, swift scale up of health communications and redeployment of the community surveillance programme. The Hopi experience in strengthening their public health systems to better confront COVID-19 may be informative to other indigenous peoples as they also respond to COVID-19 within the context of disproportionate burden. |
Detection of Rickettsia Species, and Coxiella-Like and Francisella-Like Endosymbionts in Amblyomma americanum and Amblyomma maculatum from a Shared Field Site in Georgia, United States of America.
Hensley JR , Zambrano ML , Williams-Newkirk AJ , Dasch GA . Vector Borne Zoonotic Dis 2021 21 (7) 509-516 Two abundant species of aggressive ticks commonly feed on humans in Georgia: the Gulf Coast tick (Amblyomma maculatum) and the Lone Star tick (A. americanum). A. maculatum is the primary host of Rickettsia parkeri, "Candidatus Rickettsia andeanae," and a Francisella-like endosymbiont (AmacFLE), whereas A. americanum is the primary host for R. amblyommatis, Ehrlichia chaffeensis, E. ewingii, and a Coxiella-like endosymbiont (AamCLE). Horizontal transmission of R. parkeri from A. maculatum to A. americanum by co-feeding has been described, and R. amblyommatis has been found infrequently in A. maculatum ticks. We assessed the prevalence of these agents and whether exchange of tick-associated bacteria is common between A. maculatum and A. americanum collected from the same field site. Unengorged ticks were collected May-August 2014 in west-central Georgia from a 4.14 acre site by flagging and from humans and canines traversing that site. All DNA samples were screened with quantitative PCR assays for the bacteria found in both ticks, and the species of any Rickettsia detected was identified by species-specific TaqMan assays or sequencing of the rickettsial ompA gene. Only R. amblyommatis (15) and AamCLE (39) were detected in 40 A. americanum, while the 74 A. maculatum only contained R. parkeri (30), "Candidatus Rickettsia andeanae" (3), and AmacFLE (74). Neither tick species had either Ehrlichia species. Consequently, we obtained no evidence for the frequent exchange of these tick-borne agents in a natural setting despite high levels of carriage of each agent and the common observance of infestation of both ticks on both dogs and humans at this site. Based on these data, exchange of these Rickettsia, Coxiella, and Francisella agents between A. maculatum and A. americanum appears to be an infrequent event. |
Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes.
Voss WN , Hou YJ , Johnson NV , Delidakis G , Kim JE , Javanmardi K , Horton AP , Bartzoka F , Paresi CJ , Tanno Y , Chou CW , Abbasi SA , Pickens W , George K , Boutz DR , Towers DM , McDaniel JR , Billick D , Goike J , Rowe L , Batra D , Pohl J , Lee J , Gangappa S , Sambhara S , Gadush M , Wang N , Person MD , Iverson BL , Gollihar JD , Dye J , Herbert A , Finkelstein IJ , Baric RS , McLellan JS , Georgiou G , Lavinder JJ , Ippolito GC . Science 2021 372 (6546) 1108-1112 The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma following SARS-CoV-2 infection are unknown. Proteomic deconvolution of the IgG repertoire to the spike glycoprotein in convalescent subjects revealed that the response is directed predominantly (>80%) against epitopes residing outside the receptor-binding domain (RBD). In one subject, just four IgG lineages accounted for 93.5% of the response, including an N-terminal domain (NTD)-directed antibody that was protective against lethal viral challenge. Genetic, structural, and functional characterization of a multi-donor class of "public" antibodies revealed an NTD epitope that is recurrently mutated among emerging SARS-CoV-2 variants of concern. These data show that "public" NTD-directed and other non-RBD plasma antibodies are prevalent and have implications for SARS-CoV-2 protection and antibody escape. |
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